In vivo Depiction of alpha 7 Nicotinic Receptor Loss for Cognitive Decline in Alzheimer's Disease

Background: The alpha 7 subtype of the nicotinic acetylcholine receptor (nAChR) is considered important in higher cognitive functions, and cholinergic loss underpins the pathophysiology of Alzheimer's disease (AD). However, the relationships between alpha 7 nAChR function and clinical functions or amyloid-beta (A beta) deposition remain to be explored in the living AD brain. Objective: We aimed to elucidate the relationship between alpha 7 nAChR availability in the specific cholinergic region and cognitive decline in the A beta-confirmed AD brain. Methods: Twenty AD patients and ten age-matched healthy subjects were examined. The alpha 7-nAChR availability and A beta deposition were evaluated using positron emission tomography with an alpha 7 nAChR radiotracer C-11-(R)-MeQAA and C-11-Pittsburg compound B (C-11-PiB), respectively. Semi-quantified values of tracer binding were estimated with a simplified reference tissue method for BPND of C-11-(R)-MeQAA and a tissue ratio method for SUVR of C-11-PiB. These parameters and clinical scores were compared voxel-wise using a statistical parametric mapping method. Results: The levels of C-11-(R)-MeQAA BPND in the temporal and prefrontal cholinergic projection regions were significantly lower in AD, and negative correlations were found between C-11-PiB SUVR and C-11-(R)-MeQAA BPND in the region of the nucleus basalis magnocellularis and medial prefrontal cortex. Levels of C-11-(R)-MeQAA BPND were significantly correlated with memory and frontal function scores in AD. Conclusion: The association between A beta burden and alpha 7-nAChR reduction in the basal forebrain cholinergic system was highlighted in relation to cognitive decline in AD. This suggests that A beta-linked alpha 7-nAChR reduction is clinico-pathophyisologically important for considering a good therapeutic target in AD.